Alzheimer's study finds possible cause of disease

A study using mice has uncovered a possible cause of Alzheimer’s disease, and suggests that a drug currently being investigated in human clinical trials to treat cancer could prevent the illness.

The research has been heralded as offering hope of finding new treatments for dementia.

The findings, by Duke University in America and published in the Journal of Neuroscience, are surprising, according to one of the authors, as they contradict current thinking on the disease.

The research suggests that in mice with Alzheimer’s disease certain immune cells that normally protect the brain begin abnormally to consume an important nutrient called arginine.

By blocking this process using the drug difluoromethylornithine (DFMO), memory loss and a buildup of sticky proteins known as brain plaques were prevented.

The study used a type of mouse in which a number of important genes had been swapped to make the animal’s immune system more similar to a human’s.

Senior author Carol Colton, professor of neurology at the Duke University School of Medicine, and a member of the Duke Institute for Brain Sciences, said: “If indeed arginine consumption is so important to the disease process, maybe we could block it and reverse the disease.”

It was previously thought the brain releases molecules that ramp up the immune system, apparently damaging the brain, but the study found a heightened expression of genes associated with the suppression of the immune system.

Author Matthew Kan said: “It’s surprising because [suppression of the immune system is] not what the field has been thinking is happening in AD [Alzheimer’s disease].”

Mice that had been given the drug DFMO to block arginase, an enzyme that breaks down arginine, were found to perform better in memory tests.

“All of this suggests to us that if you can block this local process of amino acid deprivation, then you can protect the mouse, at least, from Alzheimer’s disease,” Kan said.

Colton added: “We see this study opening the doors to thinking about Alzheimer’s in a completely different way, to break the stalemate of ideas in AD.”

It is thought that this year one person every three minutes will develop dementia. The disease costs the UK economy more than £26bn each year.

The research has been welcomed by the Alzheimer’s Society. Its head of research, Dr James Pickett, said: “This study in animals joins some of the dots in our incomplete understanding of the processes that cause Alzheimer’s disease, in particular around the role played by the immune system.

“Using a new animal model of Alzheimer’s, the researchers have found that depletion of a nutrient called arginine occurs in the damaged brain areas. Blocking the use of arginine reduced some of the disease hallmarks and improved memory performance, offering hope that these findings could lead to new treatments for dementia.

“Importantly, these new findings reflect earlier observations that arginine is reduced in the brains of people with Alzheimer’s disease. The next step would be to show that targeting arginine metabolism in the brain can reduce the death of brain cells, as this was not shown in the current study.”